Sedative–hypnotic effect of YZG-330 and its effect on chloride influx in mouse brain cortical cells

This study was to examine the sedative–hypnotic effect of YZG-330 and its influence on Cl−influx in mouse cortical cells.In a sleep time-prolongation test in which mice were administered a threshold dosage of sodium pentobarbital(ip),YZG-330(0.125,0.5 and 2 mg/kg,po)prolonged the sleep time by 25%(P40.05),64%(Po0.01)and 506%(Po0.001),respectively.Thereafter,treatment with YZG-330 permitted mice that had woken up after the threshold dose of sodium pentobarbital(ip)to fall asleep again.A Cl−-sensitive fluorescent probe,N-(ethoxycarbonylmethyl)-methoxyquinolinium bromide(MQAE),was used to determine the effect of YZG-330 on Cl−influx.YZG-330(0.3,0.6 and 1.5 mM)increased Cl−influx in mouse cortical cells in a concentration-dependent manner.These data suggest that YZG-330 has a hypnotic effect in mice,and the effect may be related to an increase in Cl−influx in cortical cells.

A Nucleotide-based Drug Protects Against Glutamate-and MPP^(+)-Induced Neurotoxicity

Nucleo CMP Forte? is a nucleotide-based drug consisting of cytidinemonophosphate, uridinemonophosphate, uridin-ediphosphate and uridinetriphosphate. It has been prescribed for peripheral nervous system disorders, such as lum-bosciatalgia, diabetic or alcoholic polyneuropathy, or trigeminal neuralgia. Its effects on brain pathologies has re-ceived little attention. We examined its neuroprotective effects on cell toxicity induced by glutamate excitotoxicity or by 1-methyl-4-phenyl-pyridinium (MPP+), an in vitro cell model of Parkinson’s disease. We used the human dopaminergic cell line SH-SY5Y and a primary culture of rat cortical cells pre-treated with the drug for 24 hours and then exposed to MPP+ or glutamate at a range of concentrations. Cell viability was measured at different times. Nucleo CMP Forte? pre-treatment significantly increased the rate of cell division in SH-SY5Y cells, as well as the synthesis of triglycerides and phospholipids. More interestingly, drug pre-treatment significantly reduced MPP+- and glutamate-induced cell death in SH-SY5Y cells and in rat cortical cells. These results indicate that the nucleotides included in Nucleo CMP Forte? are promising therapeutic molecules for the prevention of neuronal death in brain caused by focal ischemia, Parkinson’s disease or other neurodegenerative pathologies.

Intranasal administration of induced pluripotent stem cell-derived cortical neural stem cell-secretome as a treatment option for Alzheimer’s disease

Background Alzheimer’s disease(AD)is the most common neurodegenerative disorder in the elderly,resulting in gradual destruction of cognitive abilities.Research on the development of various AD treatments is underway;however,no definitive treatment has been developed yet.Herein,we present induced pluripotent stem cell(iPSC)-derived cortical neural stem cell secretome(CNSC-SE)as a new treatment candidate for AD and explore its efficacy.Methods We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation.Then to confirm the efficacy in vivo,CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity(5μg/g,once a week,4 weeks).The cell-mediated effects on nerve recovery,amyloid beta(Aβ)plaque aggregation,microglial and astrocyte detection in the brain,and neuroinflammatory responses were investigated.Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects.Results Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro.Furthermore,CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts.The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aβplaque accumulation.Conclusions Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential,non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.

Cell-specific pathways recruited for symbiotic nodulation in the Medicago truncatula legume

Medicago truncatula is a model legume species that has been studied for decades to understand the symbiotic relationship between legumes and soil bacteria collectively named rhizobia.This symbiosis called nodulation is initiated in roots with the infection of root hair cells by the bacteria,as well as the initiation of nodule primordia from root cortical,endodermal,and pericycle cells,leading to the development of a new root organ,the nodule,where bacteria fix and assimilate the atmospheric dinitrogen for the benefit of the plant.Here,we report the isolation and use of the nuclei from mock and rhizobia-inoculated roots for the single nuclei RNA-seq(sNucRNA-seq)profiling to gain a deeper understanding of early responses to rhizobial infection in Medicago roots.A gene expression map of the Medicago root was generated,comprising 25 clusters,which were annotated as specific cell types using 119 Medicago marker genes and orthologs to Arabidopsis cell-type marker genes.A focus on root hair,cortex,endodermis,and pericycle cell types,showing the strongest differential regulation in response to a short-term(48 h)rhizobium inoculation,revealed not only known genes and functional pathways,validating the sNucRNA-seq approach,but also numerous novel genes and pathways,allowing a comprehensive analysis of early root symbiotic responses at a cell type-specific level.

A novel strategy for producing high-performance continuous regenerated fibers with wool-like structure

We proposed a novel approach to prepare high-performance continuous regenerated keratin fibers with wool-like structure by using the cortical cells and linear keratin from wool waste as reinforcement and adhesive,respectively.The spindle-shaped cortical cells were taken from wool waste based on the different responses of cortical cells and mesenchyme in wool to the treatments of H_(2)O_(2) oxidation and ultrasonication.The linear keratin was yielded through dissolving wool waste in the green solution consisting of starch derived dithiothreitol and protein denaturant sodium dodecyl sulfate.The recycled keratin fibers were produced by wet-spinning of the mixture solution comprising of cortical cells,linear keratin and toughener poly(ethylene glycol)diacrylate,and crosslinked by glutaraldehyde and 4,4′-methylenebis-(phenyl isocyanate).The cortical cells were aligned along the regenerated fibers axis and retained quite a fewα-helical crystals of the intermediate filaments,benefitting improvement of mechanical properties.Consequently,the valuable chemical compositions and hierarchical microstructures of wool were largely inherited.Their mechanical properties,thermal stability,dyeing property,moisture absorption capability,and antistatic resistance resembled those of wool.The regenerated fibers contained 93.3 wt.%components of wool,and the amount of synthetic chemicals in the regenerated fibers was controlled to as low as 6.7 wt.%.